Back to resultsArginine Malaria Trial: Study of Adjunctive Arginine in Falciparum Malaria
Primary Purpose
Malaria, Falciparum
Status
Completed
Phase
Phase 1
Locations
Indonesia
Study Type
Interventional
Intervention
intravenous (IV) arginine
Sponsored by
About this trial
This is an interventional treatment trial for Malaria, Falciparum focused on measuring falciparum, malaria, arginine
Eligibility Criteria
Inclusion Criteria: Ages 18-60 years P. falciparum parasitemia (1,000-100,000 parasites/ul). Clinical syndrome consistent with malaria associated with documented fever (axillary temperature > 38℃) or self-reported history of fever in the last 48 hours with no other cause present Commenced oral quinine ≤ 18 hours prior to scheduled commencement of arginine An indication for hospital admission (eg relative cannot look after/supervise treatment at home but not having any warning signs or severe malaria criteria in "exclusion criteria" below) Informed consent obtained Exclusion Criteria: Pregnancy or lactation Mixed infection with P. falciparum and P. vivax Warning signs of altered mental state and inability to sit unaided Features of severe/complicated malaria Diabetes Systolic blood pressure (BP) < 100 mmHg Serious underlying disease (cardiac, hepatic, kidney) Initial iSTAT test showing any of the following values: glucose < 4 mmol/L; K+ ≥ 4.2 meq/L; Cl- > 106 meq/L; HCO3- < 20 meq/L. Known allergy to L-arginine Concurrent therapy with any of the following medications: spironolactone; oral nitrates; phosphodiesterase inhibitor (eg sildenafil [Viagra]); alpha-blocking antihypertensive agents (eg prazosin); L-arginine.
Sites / Locations
- RSMM Hospital
Outcomes
Primary Outcome Measures
exhaled and systemic nitric oxide production
endothelial function
Secondary Outcome Measures
safety
pharmacokinetic (PK) parameters
pharmacodynamic (PD) parameters
oxidant stress
gas transfer
endothelial activation
a priori subgroup analysis: endothelial function in those with baseline impairment of function
Full Information
NCT ID
NCT00147368
First Posted
September 6, 2005
Last Updated
May 30, 2008
Sponsor
Menzies School of Health Research
Collaborators
Wellcome Trust, National Health and Medical Research Council, Australia, MSHR, National Institute of Health Research and Development, Ministry of Health Republic of Indonesia, Rumah Sakit Mitra Masyarakat Hospital, University of Utah, University of Sydney
1. Study Identification
Unique Protocol Identification Number
NCT00147368
Brief Title
Arginine Malaria Trial: Study of Adjunctive Arginine in Falciparum Malaria
Official Title
Pharmacokinetic-Pharmacodynamic Study of Adjunctive Arginine in Falciparum Malaria
Study Type
Interventional
2. Study Status
Record Verification Date
May 2008
Overall Recruitment Status
Completed
Study Start Date
February 2005 (undefined)
Primary Completion Date
April 2006 (Actual)
Study Completion Date
December 2007 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Menzies School of Health Research
Collaborators
Wellcome Trust, National Health and Medical Research Council, Australia, MSHR, National Institute of Health Research and Development, Ministry of Health Republic of Indonesia, Rumah Sakit Mitra Masyarakat Hospital, University of Utah, University of Sydney
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Acute falciparum malaria is associated with low plasma arginine and impaired nitric oxide (NO) production. Both are associated with poor outcome. This study will examine the safety and effect of escalating doses of arginine in falciparum malaria. It will determine whether arginine can increase NO production and have an effect on NO-dependent physiological measurements. The hypothesis is that arginine: will be safe in falciparum malaria; will return plasma arginine concentration to normal/supranormal levels; will increase systemic and exhaled NO; reduces oxidant stress; and improves a number of NO-dependent physiological measures of relevance to malaria.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria, Falciparum
Keywords
falciparum, malaria, arginine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
intravenous (IV) arginine
Primary Outcome Measure Information:
Title
exhaled and systemic nitric oxide production
Title
endothelial function
Secondary Outcome Measure Information:
Title
safety
Title
pharmacokinetic (PK) parameters
Title
pharmacodynamic (PD) parameters
Title
oxidant stress
Title
gas transfer
Title
endothelial activation
Title
a priori subgroup analysis: endothelial function in those with baseline impairment of function
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Ages 18-60 years
P. falciparum parasitemia (1,000-100,000 parasites/ul).
Clinical syndrome consistent with malaria associated with documented fever (axillary temperature > 38℃) or self-reported history of fever in the last 48 hours with no other cause present
Commenced oral quinine ≤ 18 hours prior to scheduled commencement of arginine
An indication for hospital admission (eg relative cannot look after/supervise treatment at home but not having any warning signs or severe malaria criteria in "exclusion criteria" below)
Informed consent obtained
Exclusion Criteria:
Pregnancy or lactation
Mixed infection with P. falciparum and P. vivax
Warning signs of altered mental state and inability to sit unaided
Features of severe/complicated malaria
Diabetes
Systolic blood pressure (BP) < 100 mmHg
Serious underlying disease (cardiac, hepatic, kidney)
Initial iSTAT test showing any of the following values:
glucose < 4 mmol/L;
K+ ≥ 4.2 meq/L;
Cl- > 106 meq/L;
HCO3- < 20 meq/L.
Known allergy to L-arginine
Concurrent therapy with any of the following medications:
spironolactone;
oral nitrates;
phosphodiesterase inhibitor (eg sildenafil [Viagra]);
alpha-blocking antihypertensive agents (eg prazosin);
L-arginine.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nick M Anstey, MBBS
Organizational Affiliation
MSHR
Official's Role
Principal Investigator
Facility Information:
Facility Name
RSMM Hospital
City
Timika
Country
Indonesia
12. IPD Sharing Statement
Citations:
PubMed Identifier
17954570
Citation
Yeo TW, Lampah DA, Gitawati R, Tjitra E, Kenangalem E, McNeil YR, Darcy CJ, Granger DL, Weinberg JB, Lopansri BK, Price RN, Duffull SB, Celermajer DS, Anstey NM. Impaired nitric oxide bioavailability and L-arginine reversible endothelial dysfunction in adults with falciparum malaria. J Exp Med. 2007 Oct 29;204(11):2693-704. doi: 10.1084/jem.20070819. Epub 2007 Oct 22.
Results Reference
background
PubMed Identifier
18545693
Citation
Yeo TW, Lampah DA, Gitawati R, Tjitra E, Kenangalem E, Granger DL, Weinberg JB, Lopansri BK, Price RN, Celermajer DS, Duffull SB, Anstey NM. Safety profile of L-arginine infusion in moderately severe falciparum malaria. PLoS One. 2008 Jun 11;3(6):e2347. doi: 10.1371/journal.pone.0002347.
Results Reference
derived
Learn more about this trial
Arginine Malaria Trial: Study of Adjunctive Arginine in Falciparum Malaria
We'll reach out to this number within 24 hrs